Atherosclerosis occurs regularly at certain sites in the vessels of man and some experimental models, while other sites are spared. The bases of susceptibility and resistance may lie in the morphogenesis of the vessels. Vessels whose smooth muscle originates in the neural ectoderm are relat- ively spared, while those whose smooth muscle arises from local mesoderm are relatively susceptible; hybrid areas at the ectodermal-mesodermal interface are most susceptible. The long-term goal of this study is to determine the relationship between vessel morphogenesis and the development of atherosclerosis, using a well-described avian model. Properties that are known to be associated with atherogenesis will be compared during embryogenesis in the vessels of atherosclerosis-susceptible and resistant avian strains. Then, to test the nature of the interaction between heterogeneous vessels the ectodermal vessel primordia will be transplanted from the neural crest of atherosclerosis-prone donor embryos onto resistant recipients; and conversely. Finally, the smooth muscle cell growth-promoting capacity of ectodermal vessels will be determined. The studies proposed here will provide new data on the origin, development, structure, composition, and growth-promoting capacities of vessels of differing origins. It will be the first integrated and comprehensive study of the comparative developmental biology of genetically resistant and susceptible vessel walls. Ultimately these studies should be useful to the clinician as the relationship between developmental factors and susceptibility to atherosclerosis becomes more clearly defined.